NR4A3

This gene encodes a member of the steroid-thyroid hormone-retinoid receptor superfamily. The encoded protein may act as a transcriptional activator. The protein can efficiently bind the NGFI-B Response Element (NBRE). Three different versions of extraskeletal myxoid chondrosarcomas (EMCs) are the result of reciprocal translocations between this gene and other genes. The translocation breakpoints are associated with Nuclear Receptor Subfamily 4, Group A, Member 3 (on chromosome 9) and either Ewing Sarcome Breakpoint Region 1 (on chromosome 22), RNA Polymerase II, TATA Box-Binding Protein-Associated Factor, 68-KD (on chromosome 17), or Transcription factor 12 (on chromosome 15). Four transcript variants encoding three distinct isoforms have been identified for this gene. [provided by RefSeq]

nuclear receptor subfamily 4, group A, member 3

Transcriptional activator that binds to regulatory elements in promoter regions in a cell- and response element (target)-specific manner. Induces gene expression by binding as monomers to the NR4A1 response element (NBRE) 5'-AAAAGGTCA-3' site and as homodimers to the Nur response element (NurRE) site in the promoter of their regulated target genes (By similarity).
Plays a role in the regulation of proliferation, survival and differentiation of many different cell types and also in metabolism and inflammation. Mediates proliferation of vascular smooth muscle, myeloid progenitor cell and type B pancreatic cells; promotes mitogen-induced vascular smooth muscle cell proliferation through transactivation of SKP2 promoter by binding a NBRE site (By similarity).
Upon PDGF stimulation, stimulates vascular smooth muscle cell proliferation by regulating CCND1 and CCND2 expression. In islets, induces type B pancreatic cell proliferation through up-regulation of genes that activate cell cycle, as well as genes that cause degradation of the CDKN1A (By similarity).
Negatively regulates myeloid progenitor cell proliferation by repressing RUNX1 in a NBRE site-independent manner. During inner ear, plays a role as a key mediator of the proliferative growth phase of semicircular canal development (By similarity).
Mediates also survival of neuron and smooth muscle cells; mediates CREB-induced neuronal survival, and during hippocampus development, plays a critical role in pyramidal cell survival and axonal guidance. Is required for S phase entry of the cell cycle and survival of smooth muscle cells by inducing CCND1, resulting in RB1 phosphorylation. Binds to NBRE motif in CCND1 promoter, resulting in the activation of the promoter and CCND1 transcription (By similarity).
Plays also a role in inflammation; upon TNF stimulation, mediates monocyte adhesion by inducing the expression of VCAM1 and ICAM1 by binding to the NBRE consensus site (By similarity) (PubMed:20558821).
In mast cells activated by Fc-epsilon receptor cross-linking, promotes the synthesis and release of cytokines but impairs events leading to degranulation (By similarity).
Plays also a role in metabolism; by modulating feeding behavior; and by playing a role in energy balance by inhibiting the glucocorticoid-induced orexigenic neuropeptides AGRP expression, at least in part by forming a complex with activated NR3C1 on the AGRP- glucocorticoid response element (GRE), and thus weakening the DNA binding activity of NR3C1. Upon catecholamines stimulation, regulates gene expression that controls oxidative metabolism in skeletal muscle (By similarity).
Plays a role in glucose transport by regulating translocation of the SLC2A4 glucose transporter to the cell surface (PubMed:24022864).
Finally, during gastrulation plays a crucial role in the formation of anterior mesoderm by controlling cell migration. Inhibits adipogenesis (By similarity).
Also participates in cardiac hypertrophy by activating PARP1 (By similarity).

Animal organ regenerationIEA:Ensembl
Cellular respirationISS:UniProtKB
Cellular response to catecholamine stimulusISS:UniProtKB
Cellular response to corticotropin-releasing hormone stimulusISS:UniProtKB
Cellular response to leptin stimulusISS:UniProtKB
Common myeloid progenitor cell proliferationISS:UniProtKB
Energy homeostasisISS:UniProtKB
Fat cell differentiationISS:UniProtKB
GastrulationISS:UniProtKB
Mast cell degranulationISS:UniProtKB
Negative regulation of hydrogen peroxide-induced neuron deathISS:UniProtKB
Negative regulation of transcription by RNA polymerase IIISS:UniProtKB
Platelet-derived growth factor receptor signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of cardiac muscle hypertrophyISS:UniProtKB
Positive regulation of epithelial cell proliferationISS:UniProtKB
Positive regulation of fatty acid oxidationISS:UniProtKB
Positive regulation of feeding behaviorISS:UniProtKB
Positive regulation of glucose transmembrane transportManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of mast cell activation by Fc-epsilon receptor signaling pathwayISS:UniProtKB
Positive regulation of mast cell cytokine productionISS:UniProtKB
Positive regulation of monocyte aggregationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of smooth muscle cell proliferationISS:UniProtKB
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of vascular associated smooth muscle cell migrationManual Assertion Based On ExperimentIGI:BHF-UCL
Positive regulation of vascular associated smooth muscle cell proliferationManual Assertion Based On ExperimentIGI:BHF-UCL
Pyruvate oxidationISS:UniProtKB
Regulation of smooth muscle cell proliferationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Regulation of type B pancreatic cell proliferationISS:UniProtKB

Nucleus

Ewing sarcoma (ES):
A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors.

Phosphorylated by PRKDC.